Wearable device with tragus modulation system

ABSTRACT

A wearable device combines its existing functions (e.g., a headphone) with non-invasive autonomic modulation using tragus or other external auditory meatus stimulation. The wearable device can output audio to a user, such as music, podcast, etc., and further provide modulation of the vagus nerve via tragus stimulation or other external auditory meatus stimulation to treat various diseases.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.16/879,386 filed on May 20, 2020, which claims the benefit of U.S.Application Ser. No. 62/850,976, filed May 21, 2019. The disclosure ofthe prior applications are considered part of (and are incorporated byreference in) the disclosure of this application.

TECHNICAL FIELD

This document describes devices, systems, and methods related to tragusor other external auditory meatus modulation.

BACKGROUND

Peripheral methods to modulate the autonomic nervous system have beendone via acupuncture or acupressure. Some device-based stimulation hasbeen used in cardiac rhythm disorder treatment, as well as treating someforms of epilepsy, depression, appetite control, and a few otherdisorders. A particular branch of the vagus nerve is intracranial, andinnervates the tragus and part of the external auditory meatus. Lowlevel stimulation of the tragus has been used. However, such typicaldevices and methods of stimulation are cumbersome and not part ofeveryday use technology.

SUMMARY

Some embodiments described herein include a wearable device thatcombines its existing functions (e.g., a headphone) with non-invasiveautonomic modulation using tragus or other external auditory meatusstimulation. For example, the wearable device is configured to outputaudio to a user, such as music, podcast, etc., and further providemodulation of the vagus nerve via tragus stimulation or other externalauditory meatus stimulation to treat various diseases, such ascardiovascular, neurologic, and/or gastroenterological illnesses. Thewearable device can be worn or engaged with a non-invasive body portion,such as an external ear, an auditory canal, and other suitable bodyareas.

The wearable device can include an electroporation circuit to providetragus stimulation. In addition, the wearable device can be configuredto provide an inhibitory signal to the tragus area to detect signals andparameters for autonomic tone and transmit a reversible electroporationsequence based on the detected signals and parameters if the stimulatorysignal is found to result in, or likely to cause, an undesired effect.

The wearable device can include a filtering circuit configured toprevent the stimulatory and/or inhibitory signals from interfering withthe audio signal (e.g., music) outputted from the wearable device. Forexample, the filtering circuit can generate a signal that can cancel anoise from the stimulatory and/or inhibitory signals, thereby providingclarity in audio output from the wearable device.

The wearable device can include a validation circuit configured tovalidate that the stimulatory and/or inhibitory signals have targetedand resulted in desired physiological effects. For example, thevalidation circuit can generate a reversible electroporation signal tovalidate whether perceived signals are indeed the transmitted signals ormerely represent noise.

The wearable device can include a feedback circuit that detectsautonomic tone based on various sensor inputs, and controls generationand/or transmission of the stimulatory and/or inhibitory signals.

Particular embodiments described herein include a wearable deviceincluding a housing configured to be removably attached adjacent to atragus area; a speaker configured to generate sound based on the soundsignal; a sensor configured to detect physiological or neurologicalparameters; electrodes configured to deliver electric signals; aprocessing device; and a memory device storing instructions that whenexecuted by the processing device cause the wearable device to performoperations comprising: outputting audio using the speaker; generating astimulatory signal; applying the stimulatory signal on the tragus areato increase vagal tone; detecting a signal for autonomic tone;determining that a vagal input exceeds a threshold value; generating aninhibitory signal that represents a reversible electroporation sequence;and applying the inhibitory signal on the tragus area.

In some implementations, the system can optionally include one or moreof the following features. The stimulatory signal can be DC signal. Theinhibitory signal can be inverse to the stimulatory signal. At least oneof the stimulatory signal and the inhibitory signal can use nanosecondpulse widths and/or relatively high amplitude. At least one of thestimulatory signal and the inhibitory signal can use electroporationtargeting sensory nerves and sensory impulses from vagus afferents. Afrequency of the stimulatory signal and/or an electroporative pulse ofthe inhibitory signal can be determined based on a site to which thestimulatory signal and/or the inhibitory signal are applied. Theoperation can further include generating an inverse signal for thestimulatory signal and/or the inhibitory signal; injecting the inversesignal into the audio signal to cancel the stimulatory signal and/or theinhibitory signal to not interfere with user's auditory experience ofthe audio signal. The operation can further include creating a templatefor the stimulatory signal and the inhibitory signal, wherein theinverse signal is generated based on the template. The operation canfurther include generating a reversible electroporation sequence; andvalidating autonomic neural recordings based on the reversibleelectroporation sequence. The reversible electroporation sequence can bea small phased DC sequence. The operation can further include generatingpulsed DC sequences as a negative effector; and applying the pulsed DCsequences to temporarily and reversibly electroporate vagal afferents.The operation can further include detecting, using a sensor, apredetermined parameter representative of autonomic tone; anddetermining when to simulate, how much to stimulate, and when to blockbased on the predetermined parameter. The predetermined parameter caninclude a local electroneural and thermal conductivity. The operationcan further include detecting, using a neural network based learningalgorithm, an individual's physiological parameter; determining thatthere is an adverse detection of autonomic tone; and enabling preemptivechange in the stimulatory signal and/or the inhibitory signal. Thephysiological parameter can include a heart rate variability.

Particular embodiments described herein include a method for stimulatinga tragus. The method can include generating and outputting, using awearable device, an audio signal; generating, using the wearable device,a stimulatory signal; applying, using the wearable device, thestimulatory signal on a tragus area to increase vagal tone, wherein thewearable device is arranged at the tragus area; detecting a signal forautonomic tone; determining that a vagal input exceeds a thresholdvalue; generating, using the wearable device, an inhibitory signal thatrepresents a reversible electroporation sequence; and applying, usingthe wearable device, the inhibitory signal on the tragus area.

In some implementations, the system can optionally include one or moreof the following features. At least one of the stimulatory signal andthe inhibitory signal can use nanosecond pulse widths and/or relativelyhigh amplitude. At least one of the stimulatory signal and theinhibitory signal can use electroporation targeting sensory nerves andsensory impulses from vagus afferents. A frequency of the stimulatorysignal and/or an electroporative pulse of the inhibitory signal can bedetermined based on a site to which the stimulatory signal and/or theinhibitory signal are applied. The method can further include generatingan inverse signal for the stimulatory signal and/or the inhibitorysignal; injecting the inverse signal into the audio signal to cancel thestimulatory signal and/or the inhibitory signal to not interfere withuser's auditory experience of the audio signal. The method can furtherinclude creating a template for the stimulatory signal and theinhibitory signal, wherein the inverse signal is generated based on thetemplate. The method can further include generating a reversibleelectroporation sequence; and validating autonomic neural recordingsbased on the reversible electroporation sequence. The reversibleelectroporation sequence can be a small phased DC sequence. The methodcan further include generating pulsed DC sequences as a negativeeffector; and applying the pulsed DC sequences to temporarily andreversibly electroporate vagal afferents. The method can further includedetecting, using a sensor, a predetermined parameter representative ofautonomic tone; and determining when to simulate, how much to stimulate,and when to block based on the predetermined parameter. Thepredetermined parameter can include a local electroneural and thermalconductivity. The method can further include detecting, using a neuralnetwork based learning algorithm, an individual's physiologicalparameter; determining that there is an adverse detection of autonomictone; and enabling preemptive change in the stimulatory signal and/orthe inhibitory signal. The physiological parameter can include a heartrate variability.

The devices, system, and techniques described herein may provide one ormore of the following advantages. Some embodiments described hereininclude a wearable device with tragus or other external auditory meatusstimulation, which is for easy and daily use. Further, the wearabledevice provide a non-invasive way to perform tragus or external auditorymeatus stimulation. Moreover, the tragus or external auditory meatusstimulation is combined with music and auditory stimulation thatprovides mood altering and autonomic neural modulatory effects.

The details of one or more implementations are set forth in theaccompanying drawings and the description below. Other features andadvantages will be apparent from the description and drawings, and fromthe claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a block diagram of an example system for tragus stimulation.

FIG. 2 illustrates an example closed loop process of tragus or otherexternal auditory meatus stimulation using a wearable device.

FIG. 3 illustrates an example process of testing integrity of a signaldetected from the tragus or other external auditory meatus and filteringa noise from the detected signal.

FIG. 4 illustrates an example operation of using a sensor in thewearable device.

FIG. 5 is a conceptual diagram of a system that may be used to implementthe systems and methods described in this document is illustrated.

FIG. 6 is a block diagram of computing devices that may be used toimplement the systems and methods described in this document.

DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

FIG. 1 is a block diagram of an example system 100 for tragusstimulation. The system includes a wearable device 102 which can havevarious medical or non-medical functions. For example, the wearabledevice 102 can include electromechanical devices that produce sound,such as headphones, earplugs, earphones, earbuds or headsets. Thewearable device can be of other suitable types of wearable forms withvarious functionalities. The wearable device 102 has a housingconfigured to be worn or engaged with a suitable body portion, such as atragus area or other external auditory meatus areas. In the illustratedexample, the wearable device 102 is an earbud engageable with a tragusarea.

The wearable device 102 can communicate with a computing device 104 viavarious communications interface, such as Bluetooth, NFC, Wi-Fi, otherwireless interfaces, and/or wired interfaces. In some implementations,the computing device 104 can be used to perform at least part of theprocesses of the wearable device 102 described herein. In addition oralternatively, the computing device 104 can be used to interact with auser wearing the wearable device 102 and enable the user to provideinputs or feedbacks to the wearable device 102 or other remote computingdevices, such as a server. In addition or alternatively, the computingdevice 104 can be used provide audio (e.g., music, podcast, etc.) to thewearable device 102 so that the user can consume such audio via thewearable device 102.

The wearable device 102 can include audio circuitry 108 configured togenerate sound via, for example, a speaker 136 in the wearable device102. The wearable device 102 can receive a sound signal from a remotedevice, such as the computing device 104, and generate the sound basedon the sound signal.

The wearable device 102 can further include a tragus stimulation module110 having stimulation/inhibition circuitry 114, feedback circuitry 116,filtering circuitry 118, validation circuitry 120, and learningcircuitry 122.

The stimulation/inhibition circuitry 114 is configured to generate astimulatory signal and an inhibitory signal, which can be transmittedvia, for example, electrodes 134 of the wearable device 102. Theelectrodes 134 can be arranged at or adjacent a target body portion of auser, such as a tragus or other external auditory meatus, when thewearable device 102 is worn by the user. Other signals can also begenerated and transmitted by the stimulation/inhibition circuitry 114.

The feedback circuitry 116 can receive signals from sensors 132 that areconfigured to detect various physiological, neurological, and/or othersuitable signals and parameters. For example, the feedback circuitry 116can detect autonomic tone based on various sensor inputs from thesensors 132, and control (e.g., adjust) generation and/or transmissionof the stimulatory and/or inhibitory signals (e.g., when to stimulate,how much to stimulate, when to block, etc.).

The filtering circuitry 118 can generate and transmit a signal thatprevents the stimulatory and/or inhibitory signals from interfering withthe audio signal (e.g., music) from the audio circuitry 108. Forexample, the signal from the filtering circuitry 118 can be configuredto cancel a noise from the stimulatory and/or inhibitory signals,thereby providing clarity in audio output from the wearable device.

The validation circuitry 120 operates to validate the stimulatory and/orinhibitory signals from the stimulation/inhibition circuitry 114. Forexample, the validation circuitry 120 can validate that the stimulatoryand/or inhibitory signals have resulted in desired effects. For example,the validation circuitry 120 can generate a reversible electroporationsignal to validate whether perceived signals are indeed the transmittedsignals or merely represent noise

The learning circuitry 122 can be configured to monitor, learn, andpredict a user's physiological, neurological, and/or other parameters(e.g., heartrate variability and other sensory parameters). Suchprediction can be used to provide preemptive change in the stimulatoryand/or inhibitory signals. For example, the learning circuitry 122include a real-time neural network learning machine that, if there is anadverse detection of autonomic tone with implication being eithersusceptibility to syncope or arrhythmia, predicts and preemptivelychanges the stimulatory or inhibitory sequence, even before the actualparameter concerned drops or changes such as the onset of an arrhythmia.

The wearable device 102 can include a processing device 138 configuredto at least partially execute the processes in the wearable deviceincluding the audio circuitry 108 and the tragus stimulation module 110.The wearable device 102 can include a battery 130 to supply power to thecomponents in the wearable device.

The wearable device 102 can be implemented using at least some of thecomponents described in FIG. 5 and/or FIG. 6 below.

Referring to FIGS. 2-4, example operations of the wearable device 102are described. In particular, FIG. 2 illustrates an example closed loopprocess 200 of the tragus or other external auditory meatus stimulationusing the wearable device 102. FIG. 3 illustrates an example process 300of testing integrity of a signal detected from the tragus or otherexternal auditory meatus, and filtering a noise from the detectedsignal. FIG. 4 illustrates an example operation 400 of using a sensor inthe wearable device 102.

Referring to FIG. 2, the wearable device 102, which can be clipped onthe tragus or auditory meatus (external or internal), includes a sensorthat detects physiological, neurological, and/or other parameters fromthe area (Block 202). For example, the sensor operates to detect localelectrogram, pulse wave, or skin conductivity (Block 204), and thewearable device 102 (and/or a computing device connected to the wearabledevice 102) can analyzed the detected parameters and estimate heartratevariability, autonomic tone, heartrate, cardiac output, and/or otherparameters (Block 206). With such estimation, effector therapy can beperformed using the wearable device 102 (e.g., clip or earplugintegrated with a headphone) (Block 208). As described herein, thewearable device 102 can provide a simulation signal, which can be arapid DC pulse stimulation (Block 210). The stimulation signal can begenerated in response to decreased cardia output. The stimulation can beperformed to treat syncope, low heartrate, and/or other diseases. Thewearable device 102 can provide an inhibition signal, which can be areversible electroporation (Block 212). The inhibition signal can beused to treat hypertension. The inhibition signal can also be used totreat depression, cognitive decline, and/or other diseases. While thestimulation and/or inhibition are performed, the wearable device 102 cancontinue to use the sensor to detect the parameters (return to Block 202and subsequent Blocks). The operations of the wearable device 102 inFIG. 2 are further described herein.

Referring to FIG. 3, the wearable device 102 and/or a computing deviceconnected to the wearable device 102 can test integrity of signals fromthe tragus or external auditory meatus sensory. For example, thewearable device 102 and/or a connected computing device can retrieveelectrogram and signals sensed from the tragus or external auditorymeatus (Block 302), and analyze combined noise and true neural activity(Block 304). The wearable device 102 and/or a connected computing devicecan test a electroporation pulse (Block 306). If signals are found todecrease physiological parameters (Block 308), the signals are validatedand used for feedback (Block 310). If signals are found to increase orunchange noise (Block 312), the signals are ignored and not used forfeedback (Block 314). The operations of the wearable device 102 in FIG.3 are further described herein.

Referring to FIG. 4, the system described herein can be integrated witha variety of wearable devices (Block 402). One or more sensors can bedisposed in such wearable devices, such as ring, watch, and otherexternal wearables (Block 404). The system integrated with the wearablescan be used to detect heartrate variability, local electrograms,autonomic tones, thermoregulatory sweat, transcutaneous conductancy, andother parameters (Block 406). Such wearables can provide Bluetooth orother wireless connectivity and is configured to provide effectortherapy on integrated headphone or other devices (Block 408). Sucheffector therapy with stimulation and/or electroporation can be providedon primary wearables such as ring or watch as well. The system canfurther provide sensor crosscheck with the sensors on the tragus or inthe external auditory meatus (Block 410). The operations described inFIG. 4 are further described herein.

As described herein, some embodiments described herein include awearable device that combines an existing function (e.g., headphone)with direct autonomic modulation via tragal stimulation. The wearabledevice can be of various types with medical or non-medical functions,such as headphones, earplugs, earphones, earbuds or headsets. Thewearable device further includes circuitry for direct tragus stimulationand automated feedback from the stimulation. The feedback can beobtained based on local electrograms, skin impedance characteristics,and/or measured heartrate.

For example, the wearable device can be configured as a headphone or thelike, and include a clipped-on stimulatory electrode component for thetragus. The wearable device is configured to provide autonomicmodulation that involves standard auditory or music entering through thewearable device (e.g., earphone), along with phasic varied levelstimulation of the tragus.

The wearable device can be formed in various configurations and designs.For example, the wearable device is a headphone which covers the earcompletely and encloses through a portion of the headphone the clip orskin electrode that is in contact with the tragus. In another example,the wearable device is an earbud that is capable of vibration for directvibratory stimulation of the tragus and the external auditory meatusitself.

In some implementations, the tragus stimulatory electrode component ofthe device can be used for a standalone self-administered therapy basedon the type of disorder and the type of treatment required.

In other implementations, because the tragus stimulatory electrodecomponent is integrated with commonly used devices (e.g., earphone orheadphone), the wearable device can be administered while music or otherauditory phenomena are being experienced.

In yet other implementations, the wearable device can be a specificpairing of an auditory stimulation with tragus stimulation. For example,the type of music and the type of stimulation are specificallyengineered for a desired complimentary effect.

In yet other implementations, the tragus stimulatory clip of the devicecan record superficial skin conductance. In addition or alternatively,the device can include a specific filtering system and further recordperipheral autonomic neural activity via the electroneurograms. As aresult, a feedback loop can be set up where the autonomic tone ismonitored. Further, as a result of the level of existing autonomic tone,the type of stimulation and/or musical experience can be modulated.

In addition or alternatively, the wearable device can include severaladditional features. For example, the wearable device can include apulse wave Doppler probe to analyze the pulse waveform, automaticallycalculate heart rate variability, and/or couple this information withneural signals and skin conductance.

As described herein, some embodiments described herein provides devicesand methods for non-invasive modulation of the vagus nerve via anon-invasive and portable DC electroporation unit. This can be appliedto various diseases as described herein. Further, the utility of DCelectroporation via portable use to a non-invasive site, such as theexternal ear, the auditory canal, the vagus, etc., can be leverage fortreatment of other diseases.

Multiple diseases involving the cardiovascular, neurologic, andgastroenterological systems can be treated with the use of DCelectroporation via modulation of the nervous system, such as the vagusnerve. These often involve invasive procedures that are dangers.Further, despite invasive and direct visualization for modulation, suchinvasive procedures still may fail.

The devices and methods described herein provide means to non-invasivelystimulate modulation of the vagus nerve via DC electroporation. In someimplementations, a wearable device can be configured to incorporate a DCelectroporation unit. A wearable device (e.g., earbuds) is configured asa portable and removable device and further configured to delivertreatment in the form of DC electroporative doses. Such a device caninclude a connector for plugging in to an energy source such as a cellphone or pocket battery, and/or an interface that receives energyremotely from an energy source (e.g., via RF transmission). For example,the wearable device is configured in the form of earbuds that canconform to the outer ear canal. The earbuds can include a plurality ofelectrodes and spacing for optimal DC delivery. In another example, thewearable device is configured in the form of an ear piercing with DCelectrodes. The ear piercing can be placed in regions of interest of theear, especially the tragus of the ear. Such an ear piercing form of thewearable device can be used for short and/or long termrecording/stimulation. In yet another example, the wearable device canbe configured as a subcutaneous device which can be placed under theskin. Such wearable devices can be configured as miniaturized devices.Such wearable devices can include a rechargeable battery as a powersource. For example, wearable devices can be used with transferencedevices that can be located at desired places (e.g., in a bedroom) wherethe wearable devices can be recharged conveniently (e.g., overnightwhile sleeping).

The wearable device can be coupled to various types of energy sources,such as DC electroporation, ultrasound/sonication, radio frequency,cryoenergy, microwave energy, chemical delivery, and/or other suitableenergy sources. Such energy sources can be used simultaneously, incombination, in series, or as discrete, timed delivery.

The wearable device can include a power source (e.g., a rechargeablebattery) to power the wearable device for DC delivery. Such a powersource can be of various types, such as from a port in a cell phone, apocket battery, a rechargeable source, a recharging via RF transmission,a rechargeable unit located in a patient's bedroom for overnightcharging, and other suitable power sources.

The delivery of DC energy can be altered in a plurality of ways. Forexample, a DC energy can be delivered by changing frequency and/orduration of the DC pulse, and/or the number of the pulses. In addition,this can be connected via a feedback circuit with ongoing monitoringand/or time set delivery which can be adapted by a cell-phone controlledand algorithm based delivery mechanism. In addition, this can be apreset/pre-specified “prescription” per individual depending on thedisease and desired treatment effect.

The wearable device and/or the computing device (e.g., a mobile device)communicatively connected to the wearable device can actively monitorthe DC delivery output. For example, multiple monitoring of physiologicparameters can be performed via, e.g., the ear buds and portable unit.Such physiological parameters being monitored can include heart rate,heart rate variability, and other desired parameters. In someimplementations, such parameters can be obtained from pulsations of thecarotid or blood flow monitoring through the external ear vasculature.In addition, the wearable device (e.g., ear buds) can includefunctionality of temperature sensing, accelerometer based for activitymonitoring and positioning, and skin impedance. The monitored parametersallow for surrogacy of vagal nerve stimulation.

The wearable device can be configured to be positioned or worn invarious body locations, such as piercings of the navel, tragus, eyebrow,tongue, lip, and other suitable body locations. In addition oralternatively, the wearable device can be configured in the form of aring having an electrode so that the electrode in the ring is arrangedon a finger/thumb or toe. Alternatively or in addition, the wearabledevice can be configured in the form of a cap (e.g., baseball cap,winter hat, sweater hood, etc.) having electrodes that are arranged onsides above the ear when the cap is worn. Alternatively or in addition,the wearable can be configured in the form of a belt buckle, a shirtpocket lining, sneakers, or other suitable items.

The wearable device can include a biofeedback system for monitoringcardiac, autonomic, neurologic response, and other suitable biologicalresponses. In addition to vagal stimulation (or inhibition) circuitry,the wearable device can include a biofeedback circuitry. For example,the wearable device (e.g., earbuds) can record a far-field EEG that canbe processed for neurologic purposes. The wearable device can furtherserve as a return electrode to widen the antenna for cardiac recording.In some implementations, the earbuds can be connected via a headset withinterloping band (e.g., traditional headsets/speakerphones) in order toserve as a unit that can include multiple electrodes for EEG recordingand/or ECG for recording heart rate. The utility of these signals couldbe integrated into a feedback mechanism for input/output control,recording, transmissions, and primed for signal processing for increasedsignal recognition and deciphering. The method/algorithms can alsoinclude heart rate variability and heart rate spectral analysis.

The wearable device can be configured to provide titration with energyand/or music. For example, the wearable can deliver various tones andfrequencies of music to provide an additive effect which may permitlower doses of DC energy to be delivered. This delivery can be performedin combination, in sequence, additive/summative, and in pre-specifiedalgorithms, timing during day/night cycles.

The wearable device, such as earbuds, having DC electroporationcapability described herein can be used to treat various diseases, suchas cardia diseases (e.g., cardiac arrhythmias, heart failure, etc.),neurologic diseases (e.g., chronic dizziness/vertigo, cognitionenhancement, depression, epilepsy, autism, motion sickness, etc.),gastroentestinal diseases (e.g., chronic constipation, gastroparesisfrom diabetes, bowel mobility, weight loss, etc.), and ear/nose/throat(ENT) diseases.

For example, the wearable device is configured and used to treat cardiacarrhythmias by stimulating the vagus nerve, via the tragus, in order toinduce or inhibit vagal activity. The wearable device can be used toprovide a stimulus that can prevent, decrease the likelihood ofarrhythmias, modify the arrhythmias to a more modifiable state, orprovide an abrupt elimination/termination or vagolytic defibrillation.The wearable device can be used for those at risk, with knownarrhythmias, such as atrial fibrillation where studies have suggestedtragus/vagal manipulation may alter cardiac electrophysiology toreduce/eliminate atrial fibrillation. Further, the wearable device canbe used to cardiovert with a strong vagus input out of atrialfibrillation, as opposed to external cardiac defibrillation. Moreover,the wearable device can be used with defibrillators in place in order toincrease the efficacy of defibrillation, success of defibrillation, andpotentially defibrillation with a lower delivery of joules from the ICDcomponent.

The wearable device can be configured and used to treat heart failure byinvoking modulation of the vagus nerve in the pathogenesis and ongoingcontinuum of heart failure. Chronic, intermittent, or sequentialpulsations at various times of the day may change the overallsympathetic/parasympathetic system in order to favor more favorableheart failure stability and potentially positive remodeling.

The wearable device can be configured and used to treat chronicdizziness/vertigo. For example, the utility of having earbuds in theexternal auditory ear canal provides a vantage point to the semilunarcanals. The use of DC electroporation and/or ultrasound sonication canbe used in combination. The stimulation can be user induced whendizziness occurs. Stimulation can cause activation ofmechanotransduction receptors and hair cells, and thus facilitate themovement of endolymphatic flow and movement of otoliths/canaliths.Alternatively, sonication can be used to provide lithotripsy of theotoliths/canaliths to destroy rather than dislodge these particles whichcreate dizziness.

The wearable device can be configured and used for cognitionenhancement. For example, the stimulation of the vagus has the potentialto improve cognition and thus low-level DC stimulation of the tragus maypromote this.

The wearable device can be configured and used to treat depression. Forexample, stimulation of the vagus can be used to improve depressivesymptoms. The wearable device for cognition enhancement and depressiontreatment can also be used in combination with musical therapy toprovide additional benefits in cognition and psyche.

The wearable device can be configured and used to treat epilepsy, suchas refractory epilepsy, of which the vantage point of the tragus canprovide an ideal position.

The wearable device can be configured and used for potential therapy inautism. For example, stimulation of vagus can provide signals to higherbrain centers which can, along with incorporation with music therapy,improve cognition and function in autism.

The wearable device can be configured and used for motion sicknesstreatments. For example, cruise ship, fishing trip, long travel.Further, the wearable device can also be used for military and/or NASAspace astronauts.

The wearable device can be configured and used for gastroentestinaltreatment. For example, vagus stimulation provides a strong input to theGI tract motility. This can be of use in patients with chronicconstipation or with gastroparesis from diabetes. This can promote bowelmotility. The portability and ease of turning on therapy can make this adaily treatable condition. Further, the wearable device can be used fora weight loss strategy by using vagal stimulation/inhibition, cycling,feedback, and circadian stimulation.

The wearable device can be configured and used for ENT treatment, suchas chronic otitis externa. For example, the use of ear buds in theexternal auditory canal can deliver continuous, intermittent, or therapyregulated delivery of DC electroporation to kill bacteria in the canalthat are causative of this painful disease. This can provide an optionof intermittent sterilization rather than chronic antibiotics.

As described herein, in addition to, or alternatively to, the wearabledevice that combines a typical functionality (e.g., headphone) withdirect tragus stimulation and automated feedback based on, for example,local electrograms, skin impedance characteristics, and measuredheartrate, some embodiments described herein provide a wearable devicewhich can fit into the external auditory meatus and include acircumferential pulse sensor for measuring and/or estimating variousphysiological parameters, such as heartrate, blood pressure, oxygensaturation, cardiac stroke volume, and cardiac output. The wearabledevice can be of various types with medical or non-medical functions,such as headphones, earplugs, or headsets. The wearable device furtherincludes circuitry having the sensor, or communicatively connected tothe sensor, and configured to process signals from the sensor to obtainphysiological parameters. The wearable device can be used as a simplemonitoring device for measuring physiological parameters for users whouse the wearable device for non-medical purposes (e.g., listening tomusic). In addition, the wearable device can be used as an afferent limbto produce feedback for tragal and external auditory meatus stimulation.

In some implementations, the wearable device can include electrodesarranged as a fine grid and configured to record neural signals andautomated subtraction of far-field cardiac signals. This direct feedbackis further enhanced with small stimuli that are not meant for tragalstimulation but to assess transcutaneous impedance to even furtherrefine the feedback loop essential for the operation of the system inthe wearable device.

Configured as such, the system can be used to treat hypertension(pressure monitor), improve cardiac survival and decrease arrhythmia(heartrate variability), and to treat depression and cognition withpatient-based input and feedback.

In some implementations, the system can further include a noisecanceling module configured to generate an inverted signal based on thetragal pulse, and input the inverted signal into the wearable device(e.g., headphone) to prevent audio feedback or noise that may compromisethe listening experience.

In some implementations, the stimulation signal can be generated invarious ways, such as based on reversible electroporation, electricalfields, DC pulse, optogenetic stimulation, and/or magnetic transcranialstimulation. For example, magnetic transcranial stimulation can not onlystimulate the vagus nerve but direct cortical stimulation to achieve thefunctionalities and benefits described herein. Other sources ofstimulation may include vibration or focused ultrasound.

In addition, the system can provide continuous monitoring and establishtemplates for a particular patient and patient profile so that any inputdata serve as a learning algorithm to understand future events, predictalarming trends including with deep learning networks and automatedalert systems.

Referring still to FIGS. 1-4, the tragus stimulation system describedherein is configured to perform reversible and irreversibleelectroporation from all the iterations including the external auditorymeatus and tragus combined approaches. Instead of focusing onstimulation simply due to a perceived need to increase vagal tone as theonly source of benefit, the system described herein is configured toselectively change a particular modality in both directions, i.e.,stimulation and inhibition. With such an inhibitory arm, the system canoperate to detect signals and parameters for autonomic tone, and, basedon the detected signals and parameters, send a reversibleelectroporation sequence if a vagal input is found to be too strong toresult in syncope or even cardiac arrest. As such, for example, thesystem can respond to precipitous drops in heartrate or blood pressure.Further, the inhibitory arm of the system can effectively treat severaldiseases, such as syncope, excessive sinus bradycardia, boweldysmotility disorders, and cognitive benefit.

Further, the system can provide painless stimulatory and inhibitorydelivery for therapy by using nanosecond pulse widths and relativelyhigh amplitude. Although such small pulse widths and high amplitude maycause interference with the audio signals from the device, a filteringcircuitry described herein can prevent such interference with the audiosignals. In addition or alternatively, painless stimulatory andinhibitory delivery of the system can be performed by usingelectroporation specifically targeting sensory nerves and sensoryimpulses even from the vagus afferents that still allow sendingstimulatory signals via the autonomic fibers. For example, the disjointbetween free nerve endings and myelinated as well as unmyelinated,including c-fibers, have differences in their thresholds forelectroporation, specifically allowing only sending signals through theautonomics.

The system described herein can provide multichannel sensing andstimulatory and inhibitory outputs. For example, there may be differentrequirements for different applications, e.g., heart-relatedapplications, cognitive applications, and other applications. The systemprovides multichannel sensing so that specific sites can be stimulatedat frequencies different from, and/or inhibited with electroporativepulses different from, other sites based on the regional differences onorgan benefit from various sites of sympathetic and vagal afferents.

The system can be incorporated in audio headphones, video VR/AR devices,and other types of wearable devices, and configured to handleconflicting signals in both directions as described herein. Further, thesystem herein can provide a mechanism that ensures an audio quality of awearable device (e.g., a headphone) that incorporates the system. Forexample, signals (e.g., stimulatory and inhibitory sequences) generatedby the system incorporated in a wearable device may cause artifacts thatruin the audio experience from the wearable device. The system of thepresent disclosure includes a filtering circuit that cancels noises fromthe stimulatory and inhibitory signals, thereby providing clarity inaudio output from the wearable device. As described herein, thefiltering circuit can create a template for various pulse sequences(e.g., stimulatory and inhibitory sequences), and automatically injectan inverse signal into an audio signal from the wearable device tocancel any interference of the stimulatory signal and/or inhibitorysignal with the audio output from the wearable device. The inversesignal can be configured to make the arithmetic sum to be zero whencombined with a corresponding stimulatory and/or inhibitory signal.

In some implementations, a wearable device of the system can beconfigured to be capable of various types of wired and/or wirelessconnection, such as Bluetooth, NFC, and other suitable wirelessconnections with other devices, such as watches, monitoring devices, ECGshirts, etc. the wearable device and the other devices connected withthe wearable device can be configured to enable a patient wearing it touse and create an appropriate feedback. Further, the tragus can serve asa sensory port alone to allow for feedback effector therapies at othersites including with implanted devices.

The system described herein is configured to validate the signals bygenerating a partial stimulatory sequence to see if a desiredphysiological effect occurs, thereby validating a specific spatiallocation of nerve fibers. In some implementations, the system operatesto generate reversible electroporation as an automated or manuallyadministered test to validate whether the perceived signals are indeedgenuine or simply represent noise. For example, direct neural recordingis very difficult to filter from noise. However, if we send a smallreversible electroporation sequence, a noise will not be affectedwhereas neural signals will decrease critical validation piece for anyinvention in this area that involves feedback to work.

In addition to a wearable device (e.g., a headphone) with stimulatoryelectrodes including on the tragus and within the external auditorymeatus, the system can include balloon-based electrodes within theexternal auditory meatus to audio inputs from the headphones themselvesbeing assessed for positive or negative effects on the central nervoussystem. Further, the system can use artificial intelligence algorithmsto validate perceived signals so as to provide the feedback stimulatoryor inhibitory sequence even before they are actually required, which isa critical piece for preventing sudden death and syncope. Moreover, thesystem can include vibratory stimulators within the external auditorymeatus to secure their location by increasing in circumference anddecreasing at specified frequencies that will provide additivestimulatory or inhibitory input to what is done electrically and withelectroporation.

Alternatively or in addition, the system can use other means thanelectrical means, such as optogenics and small pulsed microwave, asstimulatory sequences. Such alternative means can reduce effects ofheadphones with transcranial magnetic stimulation on cognitiveimpairment and depression beyond what it will be doing on the tragus andexternal auditory meatus alone.

Alternatively or in addition, the system can include subcutaneouselectrodes that can be placed in the region of the tragus and controlledby a watch or more distant stimulators for both stimulation andinhibition.

Referring still to FIGS. 1-4, the tragus stimulation system includes anegative effector arm for the feedback circuit. The effector arm cansimultaneously or sequentially block vagal output quickly. For example,the tragus stimulation system can use pulsed DC sequences that serve totemporarily and reversibly electroporate the vagal afferents. Althoughthe system described here is primarily described to be used for thetragus, the negative effector arm of the system can be configured to beused for other external or internal autonomic afferent sites.

The system can provide an integrated feedback loop, which can beunsupervised and/or manually set. The system uses a variety of sensoryinputs, examples of which include a local electroneural and thermalconductivity as a direct and surrogate marker for autonomic tone to knowwhen to stimulate, how much to stimulate, and when to block. In additionto this primary sensor, the system can include a clip on the tragus aspart of a wearable device (e.g., an integrated headphone or an externalauditory meatus plug) to measure several physiological parameters, suchas heart rate variability, blood pressure, estimate cardiac output, andin real time allow the optimal amount of stimulation and uniquelyblockade.

As described herein, the system is configured to use electroporation tovalidate autonomic neural recordings. In some implementations, a veryhigh sensitivity is required to detect neural signals. In thissituation, background noise becomes an important confounding feature.However, small phased DC fields will either ameliorate or attenuateautonomic neural signals but have no effect or accentuate backgroundnoise. This mechanism of validating signals is integral for the feedbackloop to work.

As described herein, the system can provide real-time date neuralnetwork based learning of an individual's heart rate variability andother sensory parameter profile such that if there is an adversedetection of autonomic tone with implication being either susceptibilityto syncope or arrhythmia, then even before the actual parameterconcerned drops or changes such as the onset of an arrhythmia,algorithmic neural network based prediction will allow preemptive changein the stimulatory or inhibitory sequence.

As described herein, the wearable device of the system can haveconnectivity with other devices, such as watches, rings, or othersensory tools to automatically modulate the stimulatory or blockingsequence.

As described herein, the system can provide unique stimulatoryalgorithms that can be in phase or tailored with the auditory or musicalexperience the individual has from the integrated headphone.

As described herein, the system operates to filter an injection ofinverted pulsed phased waveforms so as to not interfere with theauditory experience and/or not add to the background noise.

It is understood that the same or similar devices, systems, methods, andprinciples for the tragus stimulation described herein can be used forother parts of the body including other parts of the external ear. Thisincludes forms that can expand while serving as an in-ear but within theexternal auditory meatus devices that cover the entire pinna, clips tothe pinna, and combination devices. Similarly, other external sites forvagal stimulation including the hand (e.g., Xiemen point), neck, andother body structures with forms that may include collars, rings,watches, gloves, socks, etc.

It is understood that the reversible electroporation can be used notonly as a validation method for signals, but also as a standalonetherapy. For example, delivery of a reversible electroporation can beused to treat syncope.

Referring now to FIG. 5, a conceptual diagram of a system that may beused to implement the systems and methods described in this document isillustrated. In the system, mobile computing device 510 can wirelesslycommunicate with base station 540, which can provide the mobilecomputing device wireless access to numerous hosted services 560 througha network 550.

In this illustration, the mobile computing device 510 is depicted as ahandheld mobile telephone (e.g., a smartphone, or an applicationtelephone) that includes a touchscreen display device 512 for presentingcontent to a user of the mobile computing device 510 and receivingtouch-based user inputs and/or presence-sensitive user input (e.g., asdetected over a surface of the computing device using radar detectorsmounted in the mobile computing device 510). Other visual, tactile, andauditory output components may also be provided (e.g., LED lights, avibrating mechanism for tactile output, or a speaker for providingtonal, voice-generated, or recorded output), as may various differentinput components (e.g., keyboard 514, physical buttons, trackballs,accelerometers, gyroscopes, and magnetometers).

Example visual output mechanism in the form of display device 512 maytake the form of a display with resistive or capacitive touchcapabilities. The display device may be for displaying video, graphics,images, and text, and for coordinating user touch input locations withthe location of displayed information so that the device 510 canassociate user contact at a location of a displayed item with the item.The mobile computing device 510 may also take alternative forms,including as a laptop computer, a tablet or slate computer, a personaldigital assistant, an embedded system (e.g., a car navigation system), adesktop personal computer, or a computerized workstation.

An example mechanism for receiving user-input includes keyboard 514,which may be a full qwerty keyboard or a traditional keypad thatincludes keys for the digits ‘0-9’, ‘*’, and ‘#.’ The keyboard 514receives input when a user physically contacts or depresses a keyboardkey. User manipulation of a trackball 516 or interaction with a trackpad enables the user to supply directional and rate of movementinformation to the mobile computing device 510 (e.g., to manipulate aposition of a cursor on the display device 512).

The mobile computing device 510 may be able to determine a position ofphysical contact with the touchscreen display device 512 (e.g., aposition of contact by a finger or a stylus). Using the touchscreen 512,various “virtual” input mechanisms may be produced, where a userinteracts with a graphical user interface element depicted on thetouchscreen 512 by contacting the graphical user interface element. Anexample of a “virtual” input mechanism is a “software keyboard,” where akeyboard is displayed on the touchscreen and a user selects keys bypressing a region of the touchscreen 512 that corresponds to each key.

The mobile computing device 510 may include mechanical or touchsensitive buttons 518 a-d. Additionally, the mobile computing device mayinclude buttons for adjusting volume output by the one or more speakers520, and a button for turning the mobile computing device on or off. Amicrophone 522 allows the mobile computing device 510 to convert audiblesounds into an electrical signal that may be digitally encoded andstored in computer-readable memory, or transmitted to another computingdevice. The mobile computing device 510 may also include a digitalcompass, an accelerometer, proximity sensors, and ambient light sensors.

An operating system may provide an interface between the mobilecomputing device's hardware (e.g., the input/output mechanisms and aprocessor executing instructions retrieved from computer-readablemedium) and software. Example operating systems include ANDROID, CHROME,IOS, MAC OS X, WINDOWS 7, WINDOWS PHONE 7, SYMBIAN, BLACKBERRY, WEBOS, avariety of UNIX operating systems; or a proprietary operating system forcomputerized devices. The operating system may provide a platform forthe execution of application programs that facilitate interactionbetween the computing device and a user.

The mobile computing device 510 may present a graphical user interfacewith the touchscreen 512. A graphical user interface is a collection ofone or more graphical interface elements and may be static (e.g., thedisplay appears to remain the same over a period of time), or may bedynamic (e.g., the graphical user interface includes graphical interfaceelements that animate without user input).

A graphical interface element may be text, lines, shapes, images, orcombinations thereof. For example, a graphical interface element may bean icon that is displayed on the desktop and the icon's associated text.In some examples, a graphical interface element is selectable withuser-input. For example, a user may select a graphical interface elementby pressing a region of the touchscreen that corresponds to a display ofthe graphical interface element. In some examples, the user maymanipulate a trackball to highlight a single graphical interface elementas having focus. User-selection of a graphical interface element mayinvoke a pre-defined action by the mobile computing device. In someexamples, selectable graphical interface elements further oralternatively correspond to a button on the keyboard 504. User-selectionof the button may invoke the pre-defined action.

In some examples, the operating system provides a “desktop” graphicaluser interface that is displayed after turning on the mobile computingdevice 510, after activating the mobile computing device 510 from asleep state, after “unlocking” the mobile computing device 510, or afterreceiving user-selection of the “home” button 518 c. The desktopgraphical user interface may display several graphical interfaceelements that, when selected, invoke corresponding application programs.An invoked application program may present a graphical interface thatreplaces the desktop graphical user interface until the applicationprogram terminates or is hidden from view.

User-input may influence an executing sequence of mobile computingdevice 510 operations. For example, a single-action user input (e.g., asingle tap of the touchscreen, swipe across the touchscreen, contactwith a button, or combination of these occurring at a same time) mayinvoke an operation that changes a display of the user interface.Without the user-input, the user interface may not have changed at aparticular time. For example, a multi-touch user input with thetouchscreen 512 may invoke a mapping application to “zoom-in” on alocation, even though the mapping application may have by defaultzoomed-in after several seconds.

The desktop graphical interface can also display “widgets.” A widget isone or more graphical interface elements that are associated with anapplication program that is executing, and that display on the desktopcontent controlled by the executing application program. A widget'sapplication program may launch as the mobile device turns on. Further, awidget may not take focus of the full display. Instead, a widget mayonly “own” a small portion of the desktop, displaying content andreceiving touchscreen user-input within the portion of the desktop.

The mobile computing device 510 may include one or morelocation-identification mechanisms. A location-identification mechanismmay include a collection of hardware and software that provides theoperating system and application programs an estimate of the mobiledevice's geographical position. A location-identification mechanism mayemploy satellite-based positioning techniques, base station transmittingantenna identification, multiple base station triangulation, internetaccess point IP location determinations, inferential identification of auser's position based on search engine queries, and user-suppliedidentification of location (e.g., by receiving user a “check in” to alocation).

The mobile computing device 510 may include other applications,computing sub-systems, and hardware. A call handling unit may receive anindication of an incoming telephone call and provide a user thecapability to answer the incoming telephone call. A media player mayallow a user to listen to music or play movies that are stored in localmemory of the mobile computing device 510. The mobile device 510 mayinclude a digital camera sensor, and corresponding image and videocapture and editing software. An internet browser may enable the user toview content from a web page by typing in an addresses corresponding tothe web page or selecting a link to the web page.

The mobile computing device 510 may include an antenna to wirelesslycommunicate information with the base station 540. The base station 540may be one of many base stations in a collection of base stations (e.g.,a mobile telephone cellular network) that enables the mobile computingdevice 510 to maintain communication with a network 550 as the mobilecomputing device is geographically moved. The computing device 510 mayalternatively or additionally communicate with the network 550 through aWi-Fi router or a wired connection (e.g., ETHERNET, USB, or FIREWIRE).The computing device 510 may also wirelessly communicate with othercomputing devices using BLUETOOTH protocols, or may employ an ad-hocwireless network.

A service provider that operates the network of base stations mayconnect the mobile computing device 510 to the network 550 to enablecommunication between the mobile computing device 510 and othercomputing systems that provide services 560. Although the services 560may be provided over different networks (e.g., the service provider'sinternal network, the Public Switched Telephone Network, and theInternet), network 550 is illustrated as a single network. The serviceprovider may operate a server system 552 that routes information packetsand voice data between the mobile computing device 510 and computingsystems associated with the services 560.

The network 550 may connect the mobile computing device 510 to thePublic Switched Telephone Network (PSTN) 562 in order to establish voiceor fax communication between the mobile computing device 510 and anothercomputing device. For example, the service provider server system 552may receive an indication from the PSTN 562 of an incoming call for themobile computing device 510. Conversely, the mobile computing device 510may send a communication to the service provider server system 552initiating a telephone call using a telephone number that is associatedwith a device accessible through the PSTN 562.

The network 550 may connect the mobile computing device 510 with a Voiceover Internet Protocol (VoIP) service 564 that routes voicecommunications over an IP network, as opposed to the PSTN. For example,a user of the mobile computing device 510 may invoke a VoIP applicationand initiate a call using the program. The service provider serversystem 552 may forward voice data from the call to a VoIP service, whichmay route the call over the internet to a corresponding computingdevice, potentially using the PSTN for a final leg of the connection.

An application store 566 may provide a user of the mobile computingdevice 510 the ability to browse a list of remotely stored applicationprograms that the user may download over the network 550 and install onthe mobile computing device 510. The application store 566 may serve asa repository of applications developed by third-party applicationdevelopers. An application program that is installed on the mobilecomputing device 510 may be able to communicate over the network 550with server systems that are designated for the application program. Forexample, a VoIP application program may be downloaded from theApplication Store 566, enabling the user to communicate with the VoIPservice 564.

The mobile computing device 510 may access content on the internet 568through network 550. For example, a user of the mobile computing device510 may invoke a web browser application that requests data from remotecomputing devices that are accessible at designated universal resourcelocations. In various examples, some of the services 560 are accessibleover the internet.

The mobile computing device may communicate with a personal computer570. For example, the personal computer 570 may be the home computer fora user of the mobile computing device 510. Thus, the user may be able tostream media from his personal computer 570. The user may also view thefile structure of his personal computer 570, and transmit selecteddocuments between the computerized devices.

A voice recognition service 572 may receive voice communication datarecorded with the mobile computing device's microphone 522, andtranslate the voice communication into corresponding textual data. Insome examples, the translated text is provided to a search engine as aweb query, and responsive search engine search results are transmittedto the mobile computing device 510.

The mobile computing device 510 may communicate with a social network574. The social network may include numerous members, some of which haveagreed to be related as acquaintances. Application programs on themobile computing device 510 may access the social network 574 toretrieve information based on the acquaintances of the user of themobile computing device. For example, an “address book” applicationprogram may retrieve telephone numbers for the user's acquaintances. Invarious examples, content may be delivered to the mobile computingdevice 510 based on social network distances from the user to othermembers in a social network graph of members and connectingrelationships. For example, advertisement and news article content maybe selected for the user based on a level of interaction with suchcontent by members that are “close” to the user (e.g., members that are“friends” or “friends of friends”).

The mobile computing device 510 may access a personal set of contacts576 through network 550. Each contact may identify an individual andinclude information about that individual (e.g., a phone number, anemail address, and a birthday). Because the set of contacts is hostedremotely to the mobile computing device 510, the user may access andmaintain the contacts 576 across several devices as a common set ofcontacts.

The mobile computing device 510 may access cloud-based applicationprograms 578. Cloud-computing provides application programs (e.g., aword processor or an email program) that are hosted remotely from themobile computing device 510, and may be accessed by the device 510 usinga web browser or a dedicated program. Example cloud-based applicationprograms include GOOGLE DOCS word processor and spreadsheet service,GOOGLE GMAIL webmail service, and PICASA picture manager.

Mapping service 580 can provide the mobile computing device 510 withstreet maps, route planning information, and satellite images. Anexample mapping service is GOOGLE MAPS. The mapping service 580 may alsoreceive queries and return location-specific results. For example, themobile computing device 510 may send an estimated location of the mobilecomputing device and a user-entered query for “pizza places” to themapping service 580. The mapping service 580 may return a street mapwith “markers” superimposed on the map that identify geographicallocations of nearby “pizza places.”

Turn-by-turn service 582 may provide the mobile computing device 510with turn-by-turn directions to a user-supplied destination. Forexample, the turn-by-turn service 582 may stream to device 510 astreet-level view of an estimated location of the device, along withdata for providing audio commands and superimposing arrows that direct auser of the device 510 to the destination.

Various forms of streaming media 584 may be requested by the mobilecomputing device 510. For example, computing device 510 may request astream for a pre-recorded video file, a live television program, or alive radio program. Example services that provide streaming mediainclude YOUTUBE and PANDORA.

A micro-blogging service 586 may receive from the mobile computingdevice 510 a user-input post that does not identify recipients of thepost. The micro-blogging service 586 may disseminate the post to othermembers of the micro-blogging service 586 that agreed to subscribe tothe user.

A search engine 588 may receive user-entered textual or verbal queriesfrom the mobile computing device 510, determine a set ofinternet-accessible documents that are responsive to the query, andprovide to the device 510 information to display a list of searchresults for the responsive documents. In examples where a verbal queryis received, the voice recognition service 572 may translate thereceived audio into a textual query that is sent to the search engine.

These and other services may be implemented in a server system 590. Aserver system may be a combination of hardware and software thatprovides a service or a set of services. For example, a set ofphysically separate and networked computerized devices may operatetogether as a logical server system unit to handle the operationsnecessary to offer a service to hundreds of computing devices. A serversystem is also referred to herein as a computing system.

In various implementations, operations that are performed “in responseto” or “as a consequence of” another operation (e.g., a determination oran identification) are not performed if the prior operation isunsuccessful (e.g., if the determination was not performed). Operationsthat are performed “automatically” are operations that are performedwithout user intervention (e.g., intervening user input). Features inthis document that are described with conditional language may describeimplementations that are optional. In some examples, “transmitting” froma first device to a second device includes the first device placing datainto a network for receipt by the second device, but may not include thesecond device receiving the data. Conversely, “receiving” from a firstdevice may include receiving the data from a network, but may notinclude the first device transmitting the data.

“Determining” by a computing system can include the computing systemrequesting that another device perform the determination and supply theresults to the computing system. Moreover, “displaying” or “presenting”by a computing system can include the computing system sending data forcausing another device to display or present the referenced information.

FIG. 6 is a block diagram of computing devices 600, 650 that may be usedto implement the systems and methods described in this document, aseither a client or as a server or plurality of servers. Computing device600 is intended to represent various forms of digital computers, such aslaptops, desktops, workstations, personal digital assistants, servers,blade servers, mainframes, and other appropriate computers. Computingdevice 650 is intended to represent various forms of mobile devices,such as personal digital assistants, cellular telephones, smartphones,and other similar computing devices. The components shown here, theirconnections and relationships, and their functions, are meant to beexamples only, and are not meant to limit implementations describedand/or claimed in this document.

Computing device 600 includes a processor 602, memory 604, a storagedevice 606, a high-speed interface 608 connecting to memory 604 andhigh-speed expansion ports 610, and a low speed interface 612 connectingto low speed bus 614 and storage device 606. Each of the components 602,604, 606, 608, 610, and 612, are interconnected using various busses,and may be mounted on a common motherboard or in other manners asappropriate. The processor 602 can process instructions for executionwithin the computing device 600, including instructions stored in thememory 604 or on the storage device 606 to display graphical informationfor a GUI on an external input/output device, such as display 616coupled to high-speed interface 608. In other implementations, multipleprocessors and/or multiple buses may be used, as appropriate, along withmultiple memories and types of memory. Also, multiple computing devices600 may be connected, with each device providing portions of thenecessary operations (e.g., as a server bank, a group of blade servers,or a multi-processor system).

The memory 604 stores information within the computing device 600. Inone implementation, the memory 604 is a volatile memory unit or units.In another implementation, the memory 604 is a non-volatile memory unitor units. The memory 604 may also be another form of computer-readablemedium, such as a magnetic or optical disk.

The storage device 606 is capable of providing mass storage for thecomputing device 600. In one implementation, the storage device 606 maybe or contain a computer-readable medium, such as a floppy disk device,a hard disk device, an optical disk device, or a tape device, a flashmemory or other similar solid state memory device, or an array ofdevices, including devices in a storage area network or otherconfigurations. A computer program product can be tangibly embodied inan information carrier. The computer program product may also containinstructions that, when executed, perform one or more methods, such asthose described above. The information carrier is a computer- ormachine-readable medium, such as the memory 604, the storage device 606,or memory on processor 602.

The high-speed controller 608 manages bandwidth-intensive operations forthe computing device 600, while the low speed controller 612 manageslower bandwidth-intensive operations. Such allocation of functions is anexample only. In one implementation, the high-speed controller 608 iscoupled to memory 604, display 616 (e.g., through a graphics processoror accelerator), and to high-speed expansion ports 610, which may acceptvarious expansion cards (not shown). In the implementation, low-speedcontroller 612 is coupled to storage device 606 and low-speed expansionport 614. The low-speed expansion port, which may include variouscommunication ports (e.g., USB, Bluetooth, Ethernet, wireless Ethernet)may be coupled to one or more input/output devices, such as a keyboard,a pointing device, a scanner, or a networking device such as a switch orrouter, e.g., through a network adapter.

The computing device 600 may be implemented in a number of differentforms, as shown in the figure. For example, it may be implemented as astandard server 620, or multiple times in a group of such servers. Itmay also be implemented as part of a rack server system 624. Inaddition, it may be implemented in a personal computer such as a laptopcomputer 622. Alternatively, components from computing device 600 may becombined with other components in a mobile device (not shown), such asdevice 650. Each of such devices may contain one or more of computingdevice 600, 650, and an entire system may be made up of multiplecomputing devices 600, 650 communicating with each other.

Computing device 650 includes a processor 652, memory 664, aninput/output device such as a display 654, a communication interface666, and a transceiver 668, among other components. The device 650 mayalso be provided with a storage device, such as a microdrive or otherdevice, to provide additional storage. Each of the components 650, 652,664, 654, 666, and 668, are interconnected using various buses, andseveral of the components may be mounted on a common motherboard or inother manners as appropriate.

The processor 652 can execute instructions within the computing device650, including instructions stored in the memory 664. The processor maybe implemented as a chipset of chips that include separate and multipleanalog and digital processors. Additionally, the processor may beimplemented using any of a number of architectures. For example, theprocessor may be a CISC (Complex Instruction Set Computers) processor, aRISC (Reduced Instruction Set Computer) processor, or a MISC (MinimalInstruction Set Computer) processor. The processor may provide, forexample, for coordination of the other components of the device 650,such as control of user interfaces, applications run by device 650, andwireless communication by device 650.

Processor 652 may communicate with a user through control interface 658and display interface 656 coupled to a display 654. The display 654 maybe, for example, a TFT (Thin-Film-Transistor Liquid Crystal Display)display or an OLED (Organic Light Emitting Diode) display, or otherappropriate display technology. The display interface 656 may compriseappropriate circuitry for driving the display 654 to present graphicaland other information to a user. The control interface 658 may receivecommands from a user and convert them for submission to the processor652. In addition, an external interface 662 may be provide incommunication with processor 652, so as to enable near areacommunication of device 650 with other devices. External interface 662may provided, for example, for wired communication in someimplementations, or for wireless communication in other implementations,and multiple interfaces may also be used.

The memory 664 stores information within the computing device 650. Thememory 664 can be implemented as one or more of a computer-readablemedium or media, a volatile memory unit or units, or a non-volatilememory unit or units. Expansion memory 674 may also be provided andconnected to device 650 through expansion interface 672, which mayinclude, for example, a SIMM (Single In Line Memory Module) cardinterface. Such expansion memory 674 may provide extra storage space fordevice 650, or may also store applications or other information fordevice 650. Specifically, expansion memory 674 may include instructionsto carry out or supplement the processes described above, and mayinclude secure information also. Thus, for example, expansion memory 674may be provide as a security module for device 650, and may beprogrammed with instructions that permit secure use of device 650. Inaddition, secure applications may be provided via the SIMM cards, alongwith additional information, such as placing identifying information onthe SIMM card in a non-hackable manner.

The memory may include, for example, flash memory and/or NVRAM memory,as discussed below. In one implementation, a computer program product istangibly embodied in an information carrier. The computer programproduct contains instructions that, when executed, perform one or moremethods, such as those described above. The information carrier is acomputer- or machine-readable medium, such as the memory 664, expansionmemory 674, or memory on processor 652 that may be received, forexample, over transceiver 668 or external interface 662.

Device 650 may communicate wirelessly through communication interface666, which may include digital signal processing circuitry wherenecessary. Communication interface 666 may provide for communicationsunder various modes or protocols, such as GSM voice calls, SMS, EMS, orMMS messaging, CDMA, TDMA, PDC, WCDMA, CDMA2000, or GPRS, among others.Such communication may occur, for example, through radio-frequencytransceiver 668. In addition, short-range communication may occur, suchas using a Bluetooth, WiFi, or other such transceiver (not shown). Inaddition, GPS (Global Positioning System) receiver module 670 mayprovide additional navigation- and location-related wireless data todevice 650, which may be used as appropriate by applications running ondevice 650.

Device 650 may also communicate audibly using audio codec 660, which mayreceive spoken information from a user and convert it to usable digitalinformation. Audio codec 660 may likewise generate audible sound for auser, such as through a speaker, e.g., in a handset of device 650. Suchsound may include sound from voice telephone calls, may include recordedsound (e.g., voice messages, music files, etc.) and may also includesound generated by applications operating on device 650.

The computing device 650 may be implemented in a number of differentforms, as shown in the figure. For example, it may be implemented as acellular telephone 680. It may also be implemented as part of asmartphone 682, personal digital assistant, or other similar mobiledevice.

Additionally computing device 600 or 650 can include Universal SerialBus (USB) flash drives. The USB flash drives may store operating systemsand other applications. The USB flash drives can include input/outputcomponents, such as a wireless transmitter or USB connector that may beinserted into a USB port of another computing device.

Various implementations of the systems and techniques described here canbe realized in digital electronic circuitry, integrated circuitry,specially designed ASICs (application specific integrated circuits),computer hardware, firmware, software, and/or combinations thereof.These various implementations can include implementation in one or morecomputer programs that are executable and/or interpretable on aprogrammable system including at least one programmable processor, whichmay be special or general purpose, coupled to receive data andinstructions from, and to transmit data and instructions to, a storagesystem, at least one input device, and at least one output device.

These computer programs (also known as programs, software, softwareapplications or code) include machine instructions for a programmableprocessor, and can be implemented in a high-level procedural and/orobject-oriented programming language, and/or in assembly/machinelanguage. As used herein, the terms “machine-readable medium”“computer-readable medium” refers to any computer program product,apparatus and/or device (e.g., magnetic discs, optical disks, memory,Programmable Logic Devices (PLDs)) used to provide machine instructionsand/or data to a programmable processor, including a machine-readablemedium that receives machine instructions as a machine-readable signal.The term “machine-readable signal” refers to any signal used to providemachine instructions and/or data to a programmable processor.

To provide for interaction with a user, the systems and techniquesdescribed here can be implemented on a computer having a display device(e.g., a CRT (cathode ray tube) or LCD (liquid crystal display) monitor)for displaying information to the user and a keyboard and a pointingdevice (e.g., a mouse or a trackball) by which the user can provideinput to the computer. Other kinds of devices can be used to provide forinteraction with a user as well; for example, feedback provided to theuser can be any form of sensory feedback (e.g., visual feedback,auditory feedback, or tactile feedback); and input from the user can bereceived in any form, including acoustic, speech, or tactile input.

The systems and techniques described here can be implemented in acomputing system that includes a back end component (e.g., as a dataserver), or that includes a middleware component (e.g., an applicationserver), or that includes a front end component (e.g., a client computerhaving a graphical user interface or a Web browser through which a usercan interact with an implementation of the systems and techniquesdescribed here), or any combination of such back end, middleware, orfront end components. The components of the system can be interconnectedby any form or medium of digital data communication (e.g., acommunication network). Examples of communication networks include alocal area network (“LAN”), a wide area network (“WAN”), peer-to-peernetworks (having ad-hoc or static members), grid computinginfrastructures, and the Internet.

The computing system can include clients and servers. A client andserver are generally remote from each other and typically interactthrough a communication network. The relationship of client and serverarises by virtue of computer programs running on the respectivecomputers and having a client-server relationship to each other.

While this specification contains many specific implementation details,these should not be construed as limitations on the scope of anyinventions or of what may be claimed, but rather as descriptions offeatures specific to particular implementations of particularinventions. Certain features that are described in this specification inthe context of separate implementations can also be implemented incombination in a single implementation. Conversely, various featuresthat are described in the context of a single implementation can also beimplemented in multiple implementations separately or in any suitablesub-combination. Moreover, although features may be described above asacting in certain combinations and even initially claimed as such, oneor more features from a claimed combination can in some cases be excisedfrom the combination, and the claimed combination may be directed to asub-combination or variation of a sub-combination.

Similarly, while operations are depicted in the drawings in a particularorder, this should not be understood as requiring that such operationsbe performed in the particular order shown or in sequential order, orthat all illustrated operations be performed, to achieve desirableresults. In certain circumstances, multitasking and parallel processingmay be advantageous. Moreover, the separation of various systemcomponents in the implementations described above should not beunderstood as requiring such separation in all implementations, and itshould be understood that the described program components and systemscan generally be integrated together in a single software product orpackaged into multiple software products.

Thus, particular implementations of the subject matter have beendescribed. Other implementations are within the scope of the followingclaims. In some cases, the actions recited in the claims can beperformed in a different order and still achieve desirable results. Inaddition, the processes depicted in the accompanying figures do notnecessarily require the particular order shown, or sequential order, toachieve desirable results. In certain implementations, multitasking andparallel processing may be advantageous.

What is claimed is:
 1. A method for treating or preventing atrialfibrillation of a patient, the method comprising: detecting anindication of the atrial fibrillation; and in response to the detectionof the indication of the atrial fibrillation, generating, using awearable device that is worn by the patient, a stimulatory signal,wherein the stimulatory signal is applied to a tragus area to increasevagal tone.
 2. The method of claim 1, wherein the stimulatory signaluses nanosecond pulse widths and/or relatively high amplitude.
 3. Themethod of claim 2, wherein the stimulatory signal uses electroporationtargeting sensory nerves and sensory impulses from vagus afferents. 4.The method of claim 1, wherein a frequency of the stimulatory signal isdetermined based on a site to which the stimulatory signal is applied.5. The method of claim 1, further comprising: generating an inversesignal for the stimulatory signal; and creating a template for thestimulatory signal, wherein the inverse signal is generated based on thetemplate.
 6. The method of claim 1, further comprising: generating areversible electroporation sequence comprising a small phased DCsequence.
 7. The method of claim 6, further comprising: validatingautonomic neural recordings based on the reversible electroporationsequence; generating pulsed DC sequences as a negative effector; andapplying the pulsed DC sequences to temporarily and reversiblyelectroporate vagal afferents.
 8. The method of claim 7, furthercomprising: detecting, using a neural network based learning algorithm,an individual's physiological parameter; determining that there is anadverse detection of autonomic tone; and enabling preemptive change inthe stimulatory signal and/or the inhibitory signal.
 9. The method ofclaim 8, further comprising detecting, using a sensor, a predeterminedparameter representative of autonomic tone.
 10. The method of claim 9,further comprising determining when to simulate, how much to stimulate,and when to block based on the predetermined parameter.
 11. The methodof claim 10, wherein the predetermined parameter includes a localelectroneural and thermal conductivity, and wherein the physiologicalparameter includes a heart rate variability.
 12. The method of claim 1,wherein the wearable device comprises: a housing configured to beremovably worn adjacent to the tragus area; one or more sensorsconfigured to detect physiological or neurological parameters; and oneor more electrodes configured to deliver the stimulatory signal.
 13. Themethod of claim 1, wherein the wearable device further comprises: aprocessing device; and a memory device storing instructions that whenexecuted by the processing device cause the wearable device to performthe operations of claim
 1. 14. The wearable device of claim 1, whereinthe stimulatory signal is DC signal.